Pad base for transdermal administration and needle

ABSTRACT

The object of the present invention is to provide a pad base for endermism which hardly causes bad influence on organism even if a needle fractures in the skin and remains in the MicroPatch method. It is the pad base for endermism in which a minute needle  1  is installed upright on the skin side of a patch base  2  for skin. The minute needle  1  is formed from a biodegradable resin and is composed so as to be able to be injected an administering drug in a hollow center of an axle portion (a hollow portion  3 ). Even if the injection needle fractures and remains in the skin, the minute needle  1  is decomposed in vivo because it is made of a biodegradable resin; therefore, there is little bad influence is to organism.

TECHNICAL FIELD

The present invention relates to a pad base for endermism used whenpercutaneously administrating a drug which acts on organism in vivo andan injection needle. The pad base is a portion assuming the percutaneousadministration of a drug in a pad for percutaneous medication. The padfor percutaneous medication is an article covering the pad base with,for example, a pressure-sensitive adhesive sheet from the reverse of theskin side, and the like. When the pad base for endermism is used, thepad base side is pasted on the skin.

BACKGROUND ART

The skin functions as a barrier for protecting the body and inhibits theinvasion of a foreign substance in organism. Specifically, the stratumcorneum of the outermost layer which is directly brought in contact withthe foreign substance assumes the great role as a barrier. To be sure,although the digestive tract is the same as the skin from the viewpointof being directly brought in contact with the foreign substance, thedigestive tract has no barrier of stratum corneum such as the skin, andit is rather composed of the nutritional absorptive cell having functionpositively taking in nutritional components from the foreign substance,namely foods. Both the skin and the digestive tract differ from eachother greatly in this point.

On the other hand, the skin also has a function (a function ofinsensible perspiration) of discharging, and can be considered not as asimple protective membrane but an organ having adjusting function ofpermeating substances.

By the way, intramuscular injection, oral administration andadministration from the colon by a suppository have been known as theadministration procedure of a drug to organism. A percutaneousabsorption method of administrating from the skin has been proposedfocusing attention on the above-mentioned function of the skin.According to the percutaneous absorption method, the administration isnearly indolent, the control of medication is easy, adverse reaction ishardly generated, and it is expected that the QOL (Quality Of Life) of asubject is also remarkably improved because of the convenience ofadministration mode. Further, isosorbide dinitrate, estradiol,tulobuterol, nicotine, clonidine, scopolamine, fentanyl, lidocaine andthe like in addition to nitroglycerine have been developed aspercutaneously absorptive type pharmaceuticals.

The above-mentioned percutaneously absorptive type pharmaceuticals hasadvanced the study of percutaneous absorption of a drug and it has beenclear that there were many drugs which could not be percutaneouslyabsorbed by any method in accordance with the proceeding.

Then, a method of instantaneously perforating extremely fine pores inthe skin and introducing a drug utilizing the procedure ofElectroporation which is used for introducing gene in cells; a method ofIontophoresis which introduces into the skin an ionized drug using thetechnique of electrophoresis; or an administration method combiningthese have been devised as the percutaneous absorption method nextgeneration instead of the procedure of simply diffusing and absorbing adrug from the stratum corneum into the skin in conventional methods.

As a means for perforating fine pores in the skin in like manner as theElectroporation, a MicroPatch method of bringing a pad with numeroustiny needles in contact with the skin and injecting a drug from thestinging needles site has been proposed.

To illustrate the MicroPatch method more specifically, a pad forendermism used in the MicroPatch method is equipped with a plural numberof solid-core thick and short needles (made of silicon, a metal, or aplastic) with acicular pyramids of 10 to 50 μm and a reservoir for drugsolution. When it is used, the above-mentioned needles sting the skin,gaps are broadened by vibrating the contact plane of the needles withthe skin by a vibrator (100 MHz to 2000 MHz), and the drug solution fromthe above-mentioned reservoir is designed to be invaded into the skinfrom the extremely fine pore spots of the skin (for example, refer toU.S. Pat. No. 6,183,434).

As the drug administered by the MicroPatch method, insulin, morphine,α-interferon, parthyroid hormone, erythropoietin and the like aredeveloped (Altea Therpeutics Inc., Atlanta, USA), insulin and the likehave been already under the first phase of clinical test and studies forpractical application are proceeding.

As the administration method, a non needle injection method which is incontrast to the above-mentioned method is also proposed. Concretely, amethod of administrating subcutaneously under pressuring an injectionsolution, or a method of using gas with high pressure by which thepowder of a drug is subcutaneously beaten in under high pressure, or thelike are proposed. Practically, a portion of them is alreadycommercialized.

Although these administration methods have both merits and demerits, theMicroPatch method is a superior method from the viewpoints that it doesnot require specific devices and any one can easily use it.

DISCLOSURE OF THE INVENTION

The reason why a thick needle is used in a conventional MicroPatchmethod as described above is that if a long thin minute needle is used,it may fracture easily and remain in the skin, and there is a there is afear that bad influence to organism. On the other hand, administrationby vibration is essential for a procedure using a thick short needle, asdescribed above. Accordingly, the permeation of a drug in the skin isdependent on the presence or absence of vibration, therefore a powersource and the like are essential for administration of a drug.

A thin needle is desired for mitigating pain in a usual injectionneedle, but when it is too thin, there is a fear of fracturing, and ifit fractures, there is a fear that it remains in the skin and badlyinfluences an organism.

Consequently, the present invention has been performed under theabove-mentioned circumstances, and the object is to provide a pad basefor endermism hardly exercising bad influence on organism even if aneedle fractures and remains in the skin in the MicroPatch method.Further, the object is to provide a pad base for endermism hardlyexercising bad influence on organism even if a needle fractures andremains in the skin in case of a usual injection needle.

The pad base for endermism of the present invention is characterized bya pad base for endermism comprising a minute needle installed upright onthe skin side of a patch base for skin, wherein at least the minuteneedle is composed of a biodegradable resin and formed so as to be ableto be injected an administering drug in the hollow center of axleportion, or is composed of a mixture of a biodegradable resin and anadministering drug and formed so as to be a hollow shape or a solid-coreshape. Further, in the present invention, the pad base may be those inwhich an administering drug is injected in a hollow center of an axleportion of the minute needle. Further, it may be utilized as a tube forfeeding an administering drug. The minute needle which is installedupright from the patch base is not limited to one, but may be more thanone.

As one mode of the minute needle in the pad base for endermism, a minuteneedle in which the edge is a tubular article made of a biodegradableresin and a drug can be injected in the tube is proposed. When it isused, the minute needle sting the skin by pasting the pad base forendermism on the skin and a drug in the minute needle is administratedin the skin. Further, even if the minute needle fractures and remains inthe skin, since the minute needle is made of the biodegradable resin, itis decomposed in vivo and bad influence is hardly exercised to organism.Further, the above-mentioned tubular minute needle may be composed of abiodegradable resin and an administering drug. In this case, since theminute needle itself is dissolved (decomposed) in organism, a drug isalso administrated thereby.

Further, as the mode of the minute needle, those in which both ends areclosed and a drug is sealed in the tube may be preferable. Since theminute needle is decomposed in organism, the drug sealed is discharged.In this case, the minute needle is not only composed of a biodegradableresin, but also it may be composed of a biodegradable resin and anadministering drug.

Alternatively, the minute needle composed of a biodegradable resin andan administering drug may be a solid-core needle article, and medicinalbenefits may be designed to be exhibited by a drug which is eluted fromthe minute needle itself, without involving the drug.

Further, the administration condition of a drug such as instantaneouseffect and time-release property can be also changed by variouslyselecting the content form of a drug in the minute needle from amongthose in which a drug is sealed, those in which a drug is injected in atube whose one end is opened, those in which a drug is kneaded in thebiodegradable resin of the minute needle itself, and the like.

Further, according to the pad base for endermism using the pad base ofthe present invention, as described above, percutaneous absorption canbe carried out only by pasting the pad on the skin, not depending on amedication procedure by vibration. Consequently, a power source forvibration and the like is unnecessary and it is more convenient.

Further, as the biodegradable resin, polylactic acid, polyethylenesuccinate, polybutylene succinate-adipate, polybutylenesuccinate-carbonate, polycaprolactone, polyester amide, polyestercarbonate, polyvinyl alcohol, polyhydroxybutylate, mantriose, cellulose,cellulose acetate, collagen and mixtures of two or more kinds of theseresins are recommended. In particular, polylactic acid or copolymer oflactic acid with glycolic acid is preferable. For example, copolymer oflactic acid with glycolic acid, which has been already used as medicaldrugs, is gradually hydrolyzed in tissue to be lactic acid and graduallydisappears.

Further, the above-mentioned administering drug may be either of liquid,cream, gel, suspension liquid and powder, and is not substantiallylimited excluding a drug not suitable for percutaneous administration.

The minute needle having a mixture of a biodegradable resin and anadministering drug may be prepared, for example, by kneading the drug inthe biodegradable resin and hardening it. Further, the administeringdrug which is mixed with the biodegradable resin does not always need tobe the same as the administering drug which is injected in theabove-mentioned hollow portion. For example, a drug which is easilymixed (hardly separated from the biodegradable resin) with thebiodegradable resin while exhibiting the same medicinal benefits as theadministering drug in the hollow portion may be used.

The minute needle of the present invention as described above may remainin the skin by positively folding this after being stung in the skin.When the minute needle is buried in the skin, the main body of the padbase for endermism is not peeled and medication is not interrupted;therefore a drug can be sustainably released for a long period of time.

As the size of the minute needle, it is preferable that an outerdiameter is 20 μm or more and 500 μm or less, an inner diameter is 10 μmor more and 490 μm or less, and a length is 100 μm or more and 1 mm orless.

Further, the minute needle and the patch base may be integrally formedfrom the same material. In this case, even if the patch base is pastedon the fractured minute needle, the patch base is also decomposed byorganism because it is made of a biodegradable resin or a biodegradableresin and an administering drug; therefore, bad influence is hardlyexercised.

Further, the injection needle of the present invention is characterizedin that at least the needle portion of the injection needle is composedof a biodegradable resin or composed of a mixture of a biodegradableresin and an administering drug.

Similar to above description, even if the needle portion of theinjection needle fractures and remains in the skin, the needle portionis decomposed in vivo because it is made of a biodegradable resin or abiodegradable resin and an administering drug; therefore, bad influenceis hardly exercised to organism.

As the biodegradable resin used for the injection needle, those similarto above description can be used, and in particular, polylactic acid ora copolymer of lactic acid with glycolic acid is preferably.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a sectional view for illustrating the shape of the hollowportion of the minute needle in the pad base for endermism of thepresent invention;

FIG. 2 is a view showing the pad base for endermism of an embodiment ofthe present invention;

FIG. 3 A is the microscopic photograph of the minute needle in the padbase for endermism of Example 10; and FIG. 3 B is a schematic viewthereof.

BEST MODE FOR CARRYING OUT THE INVENTION

The pad base for endermism of the present invention and the productionprocess thereof are specifically illustrated below referring thedrawings showing examples, but the present invention is not limited tothe examples illustrated. It can be also carried out by appropriatelyadding modifications within a range adaptable in the purport describedabove and later, and any of them is included in the technical scope ofthe present invention.

FIG. 2A and FIG. 2B are views showing a pad base for endermism of oneembodiment of the present invention, and FIG. 2 A is a sectional viewthereof and FIG. 2 B is an upper view. Further, the upper side in FIG. 2A is a patch face to the skin. The pad base for endermism includes a padcovered with a pressure-sensitive adhesive sheet from the reverse ofskin side (the lower side in FIG. 2 A) of the above-mentioned pad baseand is used by pasting it on the skin by the adhesion owing to theeffect of the pressure-sensitive adhesive sheet. Alternatively, a drugis occasionally administered by compressing the needle to stick the skinwithout adhesive agent.

As shown in FIG. 2, numerous minute needles 1 are installed upright on apatch base 2. The minute needles 1 are a cylindrical member with abottom in which a skin face side is opened. In the embodiment, both ofthe minute needles 1 and the patch base 2 are composed of abiodegradable resin (for example, polylactic acid). It is preferablethat the minute needles 1 and the patch base 2 are produced by integralmolding.

A drug is filled in a hollow portion 3 of the minute needle 1 by suctionfrom a drug container. When the pad base for endermism is used, it ispasted on the skin, the minute needles 1 sting an organism by pressuringthe patch base 2 and the drug in the hollow portions 3 is injected fromthe edges of the minute needles 1 in the organism.

As the shape of the minute needle 1, the minute needles 1 whose outerwall spreads and is thickened toward the patch base 2 are shown in FIG.2, but they are not limited to this and the outer wall may be straightline.

In addition, the depth of the hollow portions 3 of the minute needles 1may be deeper than those shown in FIG. 2. Concretely, as shown in FIG. 1B [sectional views for illustrating the form of the hollow portions ofthe minute needles], there may be those in which the height H of theminute needles 1 is the same as the depth L of the hollow portions 3[H=L (wholly hollow type: TYPE 2)], those in which the hollow portion 3reaches on way to the thickness h of the patch base 2 as shown in FIG. 1C [H<L<H+h (semi-penetration type: TYPE 3)], and those in which thehollow portion 3 penetrate the patch base 2 as shown in FIG. 1 D [H+h=L(whole penetration type: TYPE 4)]. Further, as shown in FIG. 1 A, thosein FIG. 2 are one in which the depth L of the hollow portion 3 isshallower than the height H of the minute needles 1 [H>L (semi-hollowtype: TYPE 1)]. It is hard to define a boundary clearly dividing theminute needles 1 and the supporting portion 2, in which the minuteneedles 1 and the patch base 2 were integrally molded, but here at,curvature shall be deemed as infinite, that is, a planar portion shallbe deemed as a boundary plane, a portion below the plane or less shallbe deemed as the patch base 2, and a portion installed upright from thisis called as the minute needles 1.

The depth of the hollow portion 3 of each of the minute needles 1 in thepad base equipped with a plural number of the minute needles 1 may bewholly the same, or those having different depths may be used incombination. Further, as shown in the above-mentioned TYPE 4 (FIG. 1 D),when the hollow portions 3 are those which penetrate the patch base 2from the minute needles 1, a drug storing vessel is provided at thereverse of skin side of the patch base 2, and a drug may be fed tocontinuously carry out the administration of a drug.

According to the pad base for endermism of the present invention, evenif the minute needles fracture and remain in the skin, they aredecomposed by organism and hardly exercise bad influence. Further, afterthe minute needles sting the skin, they can be also used by positivelyfolding the minute needles. Further, when the pad base for endermism isused, a drug can be administered without carrying out vibration as in aconventional MicroPatch method. Consequently, a power source and thelike are unnecessary and medication can be easily carried out.

Further, as the injection needle of one embodiment of the presentinvention, the needle portion is composed of a biodegradable resin (forexample, polylactic acid). The shape of the above-mentioned needleportion is similar to a usual injection needle and a thin needle isrecommended from the viewpoint of the mitigation of pain.

In the injection needle of the present invention, even if the needleportion remains in the skin, it is also decomposed by organism andhardly exercises bad influence.

EXAMPLES

The pad bases for endermism of Examples of the present invention areillustrated below together with examples of the specific productionprocess.

Examples 1 to 3

As a section bar for molding the minute needles, a section bar in whichstainless steel wires (thin metal wires) having a length of about 30 mmand a diameter φ of 280 μm were vertically inserted by 5 wires inlongitudinal and by 6 wires in a reticular pattern at an interval of 2mm in a rubber plate was prepared. Then, the edges of stainless steelwires of the above-mentioned section bar were perpendicularly brought incontact with the bottom of a stainless steel dish and, 3 ml of achloroform solution containing polylactic acid with a molecular weightof 101700 was poured in the stainless steel dish. After that, these wereleft alone, chloroform was evaporated by naturally drying and thepolylactic acid was solidified. Then, the stainless steel wires weretaken out from the stainless steel dish to obtain a pad base forendermism. Further, solutions with 5, 6 and 7% by weight as theconcentration of polylactic acid in the above-mentioned chloroformsolution containing polylactic acid were prepared, and pad bases whichwere obtained for the respective solutions were referred to as Examples1, 2 and 3.

Any of the above-mentioned Examples 1 to 3 was a pad base for endermismwhich had a plural number of the minute needles with a shape as shown inFIG. 1 D.

Examples 4 to 6

A similar section bar of the minute needles as the above-mentionedExamples 1 to 3 was used and the edges of stainless steel wires of theabove-mentioned section bar were perpendicularly brought in contact withthe bottom of a stainless steel dish. 3 ml of a chloroform solutioncontaining polylactic acid with a molecular weight of 67400 was pouredin the stainless steel dish, left alone, and the polylactic acid wassolidified by natural drying. Then, the stainless steel wires were takenout from the stainless steel dish to obtain a pad base for endermism.Further, solutions with 10, 11 and 12% by weight as the concentration ofpolylactic acid in the above-mentioned chloroform solution containingpolylactic acid were prepared, and pad bases which were obtained for therespective solutions were referred to as Examples 4, 5 and 6.

Any of the above-mentioned Examples 4 to 6 was a pad base for endermismwhich had a plural number of the minute needles with a shape as shown inFIG. 1 D.

Examples 7 to 9

A similar section bar of the minute needles as the above-mentionedExamples 1 to 3 was used and the edges of stainless steel wires of thesection bar were perpendicularly brought in contact with the bottom of astainless steel dish. 3 ml of a chloroform solution containingpolylactic acid with a molecular weight of 258700 was poured in thestainless steel dish, left alone, and the polylactic acid was solidifiedby natural drying. Then, the stainless steel wires were taken out fromthe stainless steel dish to obtain a pad base for endermism. Further,solutions with 1, 2 and 3% by weight as the concentration of polylacticacid in the above-mentioned chloroform solution containing polylacticacid were prepared, and pad bases which were obtained for the respectivesolutions were referred to as Examples 7, 8 and 9.

Any of the above-mentioned Examples 7 to 9 was a pad base for endermismwhich had a plural number of the minute needles with a shape as shown inFIG. 1 D.

Examples 10 to 12

A similar section bar of the minute needles as the above-mentionedExamples 1 to 3 was used, and the edges of stainless steel wires of theabove-mentioned section bar were arranged so as to perpendicularly standagainst the bottom while providing a little space from the bottom faceof a stainless steel dish. To a chloroform solution containingpolylactic acid with a molecular weight of 101700 (high molecular weightPLA) was added polylactic acid with a molecular weight of 10000 (lowmolecular weight PLA) in an amount of 0.1 part by weight based on theabove-mentioned high molecular weight PLA, 3 ml of the mix solution waspoured in the above-mentioned stainless steel dish, left alone so thatone side ends of the stainless steel wires were immersed, and thepolylactic acid was solidified by natural drying. Then, the stainlesssteel wires were taken out from the stainless steel dish to obtain a padbase for endermism. Further, solutions with 5, 6 and 7% by weight as theconcentration of polylactic acid in the chloroform solution of theabove-mentioned high molecular weight PLA were prepared, and pad baseswhich were obtained for the respective solutions were referred to asExamples 10, 11 and 12.

Any of the above-mentioned Examples 10 to 12 was a pad base forendermism which had a plural number of the minute needles with a shapeas shown in FIG. 1 C. The microscopic photograph (a magnificationconstant of 40-fold) of the minute needle in Example 10 obtained isshown in FIG. 3 A. Further, its schematic view is shown in FIG. 3 B.

Examples 13 to 15

A similar section bar of the minute needles as the above-mentionedExamples 1 to 3 was used, and the edges of stainless steel wires of theabove-mentioned section bar were arranged so as to perpendicularly standwhile providing a gap against the bottom of a stainless steel dish.Polylactic acid with a molecular weight of 10000 (low molecular weightPLA) in an amount of 0.1 part by weight based on the above-mentionedhigh molecular weight PLA was added to a chloroform solution containingpolylactic acid with a molecular weight of 67400 (high molecular weightPLA), 3 ml of the mix solution was injected in the above-mentionedstainless steel dish, one side ends of the stainless steel wires wereimmersed in the solution, and the solution was raised on the surface ofthe stainless steel wires, left alone, and the polylactic acid wassolidified by natural drying. Then, the stainless steel wires were drawnout and taken out from the stainless steel dish to obtain a pad base forendermism. Further, solutions with 10, 11 and 12% by weight as theconcentration of polylactic acid in the chloroform solution of theabove-mentioned high molecular weight PLA were prepared, and pad baseswhich were obtained for the respective solutions were referred to asExamples 13, 14 and 15.

Any of the above-mentioned Examples 13 to 15 was a pad base forendermism which had a plural number of the minute needles with a shapeas shown in FIG. 1 C.

Examples 16 to 18

A similar section bar of the minute needles as the above-mentionedExamples 1 to 3 was used, and the edges of stainless steel wires of theabove-mentioned section bar were arranged so as to perpendicularly standwhile providing a gap against the bottom of a stainless steel dish. To achloroform solution containing polylactic acid with a molecular weightof 258700 (high molecular weight PLA) was added polylactic acid with amolecular weight of 10000 (low molecular weight PLA) in an amount of 0.1part by weight based on the above-mentioned high molecular weight PLA, 3ml of the mix solution was injected in the above-mentioned stainlesssteel dish, one side ends of the stainless steel wires were immersed inthe solution, the solution was raised on the surface of the stainlesssteel wires, left alone, and the polylactic acid was solidified bynatural drying. Then, the stainless steel wires were drawn out and takenout from the stainless steel dish to obtain a pad base for endermism.Further, solutions with 1, 2 and 3% by weight as the concentration ofpolylactic acid in the chloroform solution of the above-mentioned highmolecular weight PLA were prepared, and pad bases which were obtainedfor the respective solutions were referred to as Examples 16, 17 and 18.

Any of the above-mentioned Examples 16 to 18 was a pad base forendermism which had a plural number of the minute needles with a shapeas shown in FIG. 1 C.

Further, the results of Examples 1 to 9 and the results of Examples 10to 18 are summarized in Table 1 and Table 2, respectively. TABLE 1Molecular weight of Concentration of polylactic acid PLA (% by weight)Example 1 101,700 5 Example 2 101,700 6 Example 3 101,700 7 Example 467,400 10 Example 5 67,400 11 Example 6 67,400 12 Example 7 258,700 1Example 8 258,700 2 Example 9 258,700 3

TABLE 2 Concentration of Molecular weight of high molecular highmolecular weight PLA weight PLA (% by weight) Example 10 101,700 5Example 11 101,700 6 Example 12 101,700 7 Example 13 67,400 10 Example14 67,400 11 Example 15 67,400 12 Example 16 258,700 1 Example 17258,700 2 Example 18 258,700 3

Since either of the pad bases (the patch base and the minute needles) ofthe above-mentioned Examples 1 to 18 is composed of polylactic acid,even if the minute needles fracture at usage and remain in the skin,they are anticipated to be biodegraded.

Examples 1 to 3 and 10 to 12 are more preferable among theabove-mentioned respective Examples from the viewpoints of the adheringamount of polylactic acid to the stainless steel wires, the quality ofmembrane, and the easiness of pulling-out of the stainless steel wires.

1. A pad base for endermism comprising a minute needle installed uprighton a skin side of a patch base for skin, wherein at least the minuteneedle is composed of a biodegradable resin and comprises a hollowcenter of axle portion in which an administering drug can be filled, oris composed of a mixture of a biodegradable resin and an administeringdrug and comprises a hollow shape or a solid-core shape.
 2. The pad basefor endermism according to claim 1, wherein the minute needle has anouter diameter of 20 μm or more and 500 μm or less, an inner diameter of10 μm or more and 490 μm or less and a length of 100 μm or more and 1 mmor less.
 3. The pad base for endermism according to claim 1, wherein thebiodegradable resin is polylactic acid or a copolymer of lactic acid andglycolic acid.
 4. The pad base for endermism according to claim 1,wherein the minute needle and the patch base are integrally made fromthe same material.
 5. The pad base for endermism according to claim 1,wherein the administering drug is filled in the hollow center of axleportion of the minute needle.
 6. An injection needle, wherein at least aneedle portion of the injection needle is composed of a biodegradableresin or composed of a mixture of a biodegradable resin and anadministering drug.
 7. The injection needle according to claim 6,wherein the biodegradable resin is polylactic acid or a copolymer oflactic acid and glycolic acid.
 8. The pad base for endermism accordingto claim 2, wherein the biodegradable resin is polylactic acid or acopolymer of lactic acid and glycolic acid.
 9. The pad base forendermism according to claim 2, wherein the minute needle and the patchbase are integrally made from the same material.
 10. The pad base forendermism according to claim 3, wherein the minute needle and the patchbase are integrally made from the same material.
 11. The pad base forendermism according to claim 2, wherein the administering drug is filledin the hollow center of axle portion of the minute needle.
 12. The padbase for endermism according to claim 3, wherein the administering drugis filled in the hollow center of axle portion of the minute needle. 13.The pad base for endermism according to claim 4, wherein theadministering drug is filled in the hollow center of axle portion of theminute needle.